@article{3d5abda4ebf1440cb5654fa8bd592de9,
title = "Evaluation of Urea-Based Inhibitors of the Dopamine Transporter Using the Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis",
abstract = "The dopaminergic system is involved in the regulation of immune responses in various homeostatic and disease conditions. For conditions such as Parkinson{\textquoteright}s disease and multiple sclerosis (MS), pharmacological modulation of dopamine (DA) system activity is thought to have therapeutic relevance, providing the basis for using dopaminergic agents as a treatment of relevant states. In particular, it was proposed that restoration of DA levels may inhibit neuroinflammation. We have recently reported a new class of dopamine transporter (DAT) inhibitors with high selectivity to the DAT over other G-protein coupled receptors tested. Here, we continue their evaluation as monoamine transporter inhibitors. Furthermore, we show that the urea-like DAT inhibitor (compound 5) has statistically significant anti-inflammatory effects and attenuates motor deficits and pain behaviors in the experimental autoimmune encephalomyelitis model mimicking clinical signs of MS. To the best of our knowledge, this is the first study reporting the beneficial effects of DAT inhibitor-based treatment in animals with induced autoimmune encephalomyelitis, and the observed results provide additional support to the model of DA-related neuroinflammation.",
keywords = "dopamine, dopamine transporter inhibitor, modafinil, multiple sclerosis, neuroinflammation",
author = "Md Ashraf-Uz-Zaman and Guangchen Ji and Dalton Tidwell and Linda Yin and Smathorn Thakolwiboon and Jie Pan and Riley Junell and Zach Griffin and Sadisna Shahi and Derek Barthels and Sajib, {Md Sanaullah} and Trippier, {Paul C.} and Mikelis, {Constantinos M.} and Hiranmoy Das and Mirla Avila and Volker Neugebauer and German, {Nadezhda A.}",
note = "Funding Information: Ki determinations and receptor binding profiles were generously provided by the National Institute of Mental Health{\textquoteright}s Psychoactive Drug Screening Program, Contract # HHSN-271-2013-00017-C (NIMH PDSP). The NIMH PDSP is Directed by Bryan L. Roth MD, Ph.D. at the University of North Carolina at Chapel Hill, and Project Officer Jamie Driscoll at NIMH, Bethesda MD, USA. This work was supported by the NIH 1R15CA231339-0 to N.G. and C.M., CPRIT RP170003 and RP210154 to N.G., NS038261 and NS106902 to V.N., NS109255 to GJ, South Plains Foundation grant to M.A. and V.N. Funding Information: Ki determinations and receptor binding profiles were generously provided by the National Institute of Mental Health?s Psychoactive Drug Screening Program, Contract # HHSN-271-2013-00017-C (NIMH PDSP). The NIMH PDSP is Directed by Bryan L. Roth MD, Ph.D. at the University of North Carolina at Chapel Hill, and Project Officer Jamie Driscoll at NIMH, Bethesda MD, USA. This work was supported by the NIH 1R15CA231339-0 to N.G. and C.M., CPRIT RP170003 and RP210154 to N.G., NS038261 and NS106902 to V.N., NS109255 to GJ, South Plains Foundation grant to M.A. and V.N. Publisher Copyright: {\textcopyright} 2022 American Chemical Society",
year = "2022",
month = jan,
day = "19",
doi = "10.1021/acschemneuro.1c00647",
language = "English (US)",
volume = "13",
pages = "217--228",
journal = "ACS Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",
number = "2",
}